DESCRIPTION: (Investigator's Abstract). Corneal transplantation is the most common and most successful form of solid organ human transplantation. Despite this success a sizeable minority of such grafts performed each year are subject to complications resulting in opacification of the grafted tissue and loss of vision. Improvement of these outcomes will require a better understanding of the underlying mechanisms of graft failure and the elucidation of methods for altering these mechanisms. Our preliminary studies using a rat model indicate that the phenomenon of anterior chamber associated immune deviation (ACAID) may be useful in regulating the immunological reaction in corneal allograft recipients. The studies proposed in this application are designed to obtain a better understanding of the ACAID phenomenon as induced by allogeneic lymphocytes in recipients of corneal grafts. Optimal conditions for inducing ACAID will be determined by studying the fate of orthotopically placed full-thickness penetrating keratoplasties on rats injected previously into the anterior chamber of the eye with allogeneic lymphocytes. These studies will be followed by experiments designed to determine the mechanism by which an anterior chamber injection of foreign lymphocytes leads to unresponsiveness. These investigations, using both in vivo and in vitro techniques, will determine if this unresponsiveness is due to clonal deletion, induction of suppressor cells, or alteration of the idiotype-antiidiotype network. It is anticipated that the results obtained from these experiments will enhance our understanding of the inter-connections between the immune system and the eye, and may lead to the development of new procedures to pretreat corneal graft recipients at high risk of graft failure.